1. Field of the Invention
This invention relates to novel peptides, intermediates therefor, process for preparing the same, and antiallergic agents, vasodilators and immunoregulators.
2. Description of Prior Art
A variety of drugs have been proposed and developed for the prevention or therapy of various allergic diseases. Some of them have already been placed on the market.
Among the allergic symptoms, immediate-type allergic reactions such as bronchial asthma, urticaria and allergic rhinitis are classified as type I-allergic reaction. The type I-allergic reaction is in general believed on the basis of onset of the symptoms and action mechanism of the antiallergic agent to involve the following three stages: First, interaction among macrophage, T cell and B cell against an extraneous antigen which has entered the body produces IgE antibody, which is fixed to the Fc receptor in tissue mast cells or blood basophils thereby producing sensitization (this process is at the first stage; next, when the extraneous antigen again enters the body, the IgE antibody fixed to the Fc receptor in the cells and the extraneous antigen are bonded to cause antigen-antibody reaction which triggers such reactions as activation of the cell membrane enzymes and inflow of calcium ions into cells thereby producing biochemical changes such as enzymatic reactions and histological changes such as degranulation with a result that chemical mediators such as histamine and SRS-A are released outside the cells (this process is at the second stage); the chemical mediators released outside the cells at the second stage have such actions as contraction of smooth muscles and accentuation of permeability and promotion of excretion of the capillary blood vessels and cause various allergic symptoms (this process is at the third stage).
Known antiallergic agents include those for nonspecific hyposensitization therapy as well as for inhibition of antibody production, which are durgs acting on the first stage. None of the drugs specifically acting on the first stage only has been placed on the market. As drugs acting on the second stage are known chemical mediator-inhibitory agents such as disodium cromoglycate (called cromoglycate for short hereinbelow) and Tranilast. Antihistaminics and bronchodilators are drugs acting on the third stage.
Furthermore, there are disclosed antiallergic peptides in U.S. Pat. No. 4,171,299. In the specification is included an IgE antibody-originated pentapeptide composed of five amino acid residues of the Fc portion of IgE antibody as represented by the primary structure EQU H-Asp-Ser-Asp-Pro-Arg-OH.
Inhibition of the IgE antibody production by the peptide has not been confirmed. However, it is believed that the peptide blocks allergic reaction by inhibiting binding of the IgE antibody with mast cells which occurs at the beginning of the second stage, as well as by simultaneously substituting the bound IgE antibody already formed at the second stage with the peptide.
Development of antiallergic agents has heretofore been directed to a drug acting on one of the three stages for the onset of allergic symptoms. Studies were made of prevention of onset or therapeutic treatment of allergic symptoms by blocking at any one stage in the chain of the three stages. Therapy which is expected to produce some efficacy has been developed by such approach.
These known chemotherapeutic agents, however, cannot completely block the chain of the above-mentioned three stages. Consequently, use of a combination of several drugs has been adopted based on an idea of realizing complete blocking of the chain by combined use of a drug acting on one of the three stages with a drug acting on another, but the results are not as expected.
Then, it is expected that development of a single drug acting on plural stages of the three stages in the onset of allergic symptoms would enhance the effects as an antiallergic agent, and development of such drugs is desirable.
It is also conceivable on the basis of mechanism of the onset of allergic symptoms that superior antiallergic agents would become available if a peptide of the Fc portion of IgE antibody origin or a peptide analogous to such peptide is developed. Development of novel peptides by such approach is also expected
It is an object of this invention to provide antiallergic peptides with superior pharmacological activities by preparing a peptide of the Fc portion of IgE antibody or a peptide analogous thereto.